, Volume 73, Issue 2, pp 120–125 | Cite as

Effects of lithium on behavioral reactivity: Relation to increases in brain cholinergic activity

  • Roger W. Russell
  • Robert Pechnick
  • Richard S. Jope
Original Investigations


Suppression of behavior accompanying increased ACh synthesis in the brain might account, at least in part, for the preferred use of lithium in antimanic therapy. Three experiments using rats as subjects were designed to test hypotheses about relationships among lithium, ACh synthesis and behavior. Experiment 1 established that hyporeactivity and greater exploratory behavior occurred in animals under LiCl treatment conditions shown to stimulate cholinergic activity in brain. Experiment 2 provided evidence of significant differences between controls and animals on the LiCl diet. Groups tested after 1 or 2 days of LiCl showed the decrease in reactivity to successive presentations of a loudd auditory stimulus which characterizes the normal process of habituation. Groups tested after 5 or 10 days of LiCl showed no evidence of habituation, their reactivity throughout the period of stimulation being at a level attained by the other groups when habituation reached its final asymptote. Experiment 3 established that effects of LiCl treatment were not manifested in all aspects of behavior: there was no evidence of impairment of motor activity or coordination; no analgesia; no impairment in sensory input nor in acquisition of new behaviors. The effect of the LiCl treatment was not complete inhibition but instead suppression of reactivity to environmental stimulation under conditions shown previously to increase cholinergic activity in brain.

Key words

Lithium Acetylcholine Cholinergic activity Mania Habituation Exploratory behavior Reactivity 


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  1. Anderson DK, Prockop LD (1975) Lithium absorption and distribution in body tissues. In: Johnson FN (ed) Lithium research and therapy. Academic Press, London, pp 267–280Google Scholar
  2. Banks A, Russell RW (1967) Effects of chronic reductions in acetylocholinesterase activity on serial problem-solving behavior. J Comp Physiol Psychol 64:262–267Google Scholar
  3. Berger PA, Davis KL, Hollister LE (1979) Cholinomimetics in mania, schizophrenia and memory disorders. In: Barbeau A, Growdon JJ, Wurtman RJ (eds) Nutrition and the brain, vol. V. Raven Press, New York, pp 425–441Google Scholar
  4. Berlyne DE (1950) Novelty and curiosity as determinats of exploratory behavior. Br J Psychol 41:68–80Google Scholar
  5. Carlton PL (1963) Cholinergic mechanisms in the control of behavior by the brain. Psychol Rev 70:19–39Google Scholar
  6. Carlton PL (1968) Brain acetylcholine and habituation. Prog Brain Res 28:48–60Google Scholar
  7. Davies C, Sanger DJ, Steinberg H, Tomkiewiez M, U'Prichard DC (1974) Lithium and α-methyl-p-tyrosine prevent “manic” activity in rodents. Psychopharmacology 36:263–274Google Scholar
  8. Denenberg VH (1969) Open-field behavior in the rat: What does it mean? Ann NY Acad Sci USA 159:852–859Google Scholar
  9. Ehrlich BE, Diamond JM (1980) Lithium, membranes and manicdepressive illness. J Membr Biol 52:187–200Google Scholar
  10. Gershon S, Shopsin B (1973) Lithium: Its role in psychiatric research and treatment. Plenum, New YorkGoogle Scholar
  11. Groves PM, Thompson RF (1970) Habituation: A dual-process theory. Psychol Rev 77:419–450Google Scholar
  12. Harris CM, Davis JM, Janowsky DS (1979) The use of cholinergic drugs in mental illness. In: Barbeau A, Growdon JH, Wurtman RJ (eds) Nutrition and the brain. Raven, New York, pp 397–408Google Scholar
  13. Ho AK, Singer G, Gershon S (1971) Biochemical evidence of adrenergic interaction with cholinergic function in the central nervous system of the rat. Effects of norepinephrine. Psychophamacologia 21:238–246Google Scholar
  14. Janowsky DS, El-Yousef MK, Davis JM, Sekerke HJ (1972) A cholinergic-adrenergic hypothesis of mania and depression. Lancet II:632–635Google Scholar
  15. Janowsky DS, El-Yousef MK, Davis JM, Sekerle HJ (1973) Parasympathetic suppression of manic symptoms by physostigmine. Arch Gen Psychiatry 28:542–547Google Scholar
  16. Johnson FN (1979) The psychopharmacology of lithium. Neurosci Biobehav Rev 3:15–30Google Scholar
  17. Jope RS (1979) Effects of lithium treatment in vitro and in vivo on acetylcholine metabolism in rat brain. J Neurochem 33:487–495Google Scholar
  18. Kerry RJ (1975) The management of patients receiving lithium treatment. In: Johnson FN (ed) Lithium research and therapy. Academic Press, London, p 148Google Scholar
  19. Leyland M, Robbins T, Iversen SD (1976) Locomotor activity and exploration: The use of traditional manipulations to dissociate these two behaviors in the rat. Anim Learning Behav 4:261–265Google Scholar
  20. Myer JS (1971) Some effects of non-contingent aversive stimulation. In: Brush FR (ed) Aversive conditioning and learning. Academic Press, New York, pp 464–536Google Scholar
  21. Olton DS, Gage FH (1976) Behavioral anatomical and biochemical aspects of septal hyperactivity. In: DeFrance JF (ed) The septal nuclei. Plenum, New York, pp 507–527Google Scholar
  22. Overstreet DH (1977) Pharmacological approaches to habituation of the acoustic startle response in rats. Physiol Psychol 5:230–238Google Scholar
  23. Russell RW (1958) Effects of “biochemical lesions” on behavior. Acta Psychol 14:281–294Google Scholar
  24. Russell RW (1966) Biochemical substrates of behavior. In: Russell RW (ed) Frontiers in physiological psychology. Academic Press, New York, pp 185–246Google Scholar
  25. Russell RW (1977) Chollnergic substrates of behavior. In: Jenden DJ (ed) Cholinergic mechanisms and psychopharmacology. Plenum Press, New York, pp 709–731Google Scholar
  26. Russell RW, Macri J (1978) Some behavioral effects of supressing choline transport by cerebroventricular injection of hemicholinium-3. Pharmacol Biochem Behav 8:399–403Google Scholar
  27. Russell RW, Macri J (1979) Central cholinergic involvement in behavioral hyper-reactivity. Pharmacol Biochem Behav 10:43–48Google Scholar
  28. Russell RW, Watson RHJ, Frankenhaeuser M (1961) Effects of chronic reductions in brain cholinesterase activity on acquisition and extinction of a conditioned avoidance response. Scand J Physiol 2:21–29Google Scholar
  29. Schou M (1976) Pharmacology and toxicology of lithium. Ann Rev Pharmacol 16:231–243Google Scholar
  30. Thomsen J, Olsen O (1974) Long-term lithium administration to rats. Int Pharmacopsychiatry 9:118–124Google Scholar
  31. Warburton DM (1975) Brain, behavior and drugs. John Wiley and Sons, London, pp 66–82Google Scholar

Copyright information

© Springer-Verlag 1981

Authors and Affiliations

  • Roger W. Russell
    • 1
    • 2
  • Robert Pechnick
    • 1
    • 2
  • Richard S. Jope
    • 1
    • 2
  1. 1.Department of Pharmacology, School of MedicineUniversity of CaliforniaLos AngelesUSA
  2. 2.the Brain Research InstituteUniversity of CaliforniaLos AngelesUSA

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